What is alpha-1-antitrypsin deficiency?
The severity of symptoms ranges from no or mild symptoms to life-threatening conditions. A cure is only possible with a liver transplant. However, this carries high risks and is only considered for life-threatening conditions. Nowadays, this disorder of the body’s metabolism can be managed well by adapting behavior and treating it with medication.
Alpha-1-antitrypsin is a protein that inhibits the activity of various endogenous enzymes. If not enough alpha-1-antitrypsin is produced due to an unfavorable gene combination inherited from the parents, the effect of various enzymes in numerous parts of the body can no longer be controlled. This mainly causes damage to the lungs, but sometimes the liver is also affected. Smoking is a major risk factor. It is possible that an affected person suffers from alpha-1-antitrypsin deficiency, but in a milder form, so that under normal circumstances no tissue damage and thus life restrictions would occur. Due to a number of unfavorable factors, the most serious of which is smoking, the protein deficiency, which was originally not a serious problem, can now lead to various, sometimes drastic, symptoms.
Alpha-1-antitrypsin deficiency – history and classification
A mutation (i.e. a permanent change) in the genetic material at the site that influences the alpha-1-antitrypsin balance is not uncommon. Nevertheless, such a genetic deviation does not always have to lead to noticeable physical limitations or clinical pictures. Rather, mutations can also be a real evolutionary advantage. A change in genetic material is not always a change for the worse. Studies suggest that mutations in the human genome that affect alpha-1-antitrypsin have accompanied human development since the Iron Age (i.e. for over 2000 years). Alpha-1-antitrypsin deficiency can also have short-term positive aspects for the person affected. Since the life expectancy of people has been considerably increased by various factors, medicine has been dealing with alpha-1-antitrypsin deficiency as a disease that causes considerable damage in the longer term.
Alpha-1-antitrypsin deficiency: causes and risk factors
Alpha-1-antitrypsin is a so-called proteinase inhibitor (enzyme inhibitor). A proteinase is an enzyme, a substance produced by the body that supports, accelerates or even enables certain processes. Alpha-1-antitrypsin inhibits the function of enzymes, especially trypsin and neutrophil elastase. In the lungs, foreign bodies (e.g. dust particles or germs) are combated by white blood cells, for example by releasing neutrophil elastase to eliminate the foreign body. The quantity and lifespan of these basically useful enzymes is regulated by alpha-1-antitrypsin.
A faulty gene sequence that causes the defect has now been identified, and different types of these deviations trigger different disease progressions. If a child inherits the genetic defect from both parents (homozygous form), the consequences of alpha-1-antitrypsin deficiency are more severe than if only the father or mother has passed on the genetic defect (heterozygous form).
The positive side of alpha-1-antitrypsin deficiency is that enzymes can fight infections of the respiratory tract unhindered and thus effectively. The danger, however, is that they also destroy healthy tissue and damage the body itself unhindered over a long period of time. This leads to restriction and degradation of the alveoli, particularly in the lungs. This may result in emphysema, which is caused by impaired gas exchange and subsequent oxygen deficiency in the body. Similar processes can lead to liver cirrhosis. The likelihood that an inherited alpha-1-antitrypsin deficiency will lead to significant damage increases with the additional stresses to which the body is exposed, such as smoking, frequent infections, poor air quality and a generally unhealthy lifestyle.
Symptoms: Alpha-1-antitrypsin deficiency
Alpha-1-antitrypsin deficiency affects metabolic processes throughout the body. However, particularly severe symptoms occur primarily in the lungs and also in the liver. The signs of a damaged lung first appear during exertion and later also at rest. Typical features are
- Shortness of breath
- Panting
- Whistling noise when breathing
- Cough
- Ejection
- Pulmonary emphysema (over-inflation of the lungs: dry irritating cough, blue coloration of the skin (cyanosis) due to lack of oxygen)
- Recurrent infections of the respiratory tract e.g. chronic bronchitis
- General disturbance of gas exchange and oxygen deficiency: fatigue, tiredness, reduced performance, impaired concentration, memory
These symptoms are also summarized under the term chronic obstructive pulmonary disease(COPD); similar to asthma, COPD is a combination of different characteristics, the causes of which can be varied. In the worst case, such a serious lung disease can progress to the point where respiratory failure, heart failure or even multiple organ failure can occur. Alpha-1-antitrypsin deficiency usually becomes noticeable after the age of 30 and the symptoms become progressively more frequent and severe. In addition to the lungs, which are mainly affected, the liver can also be damaged by the lack of sufficient enzyme inhibitors.
Already after birth, around ten percent of newborns with alpha-1-antitrypsin deficiency suffer from inflammation of the liver with jaundice. Fortunately, this often heals itself after a few weeks. In addition to massive lung damage with emphysema and postnatal liver inflammation, chronic hepatitis and even liver cirrhosis can occur at an advanced age. Liver cancer develops in around 15 percent of cases of chronic inflammation of the liver. Even more rarely, painful lumps can form in the fatty tissue of the subcutaneous tissue. In addition, an alpha-1-antitrypsin deficiency may lead to kidney failure, vascular inflammation or inflammation or scarring of the pancreas.
Alpha-1-antitrypsin deficiency: diagnosis with us
Although the disease is the second most common cause of emphysema after smoking, it is not easy to diagnose. The ambiguity of the lung symptoms does not initially suggest a more serious illness. In the case of smokers, we first assume that the addiction is the trigger for the lung problems, which is only partly true in the case of alpha-1-antitrypsin deficiency.
If you experience the symptoms described, you can give us an initial indication. We can then arrange for a blood test to measure the amount of alpha-1-antitrypsin present. The normal concentration of the enzyme inhibitor is between 150 and 300 mg/dl (milligrams per deciliter). If the value is below 90 mg/dl, this is referred to as a clear alpha-1-antitrypsin deficiency; at less than 50 mg/dl, severe lung damage is often already present. If the person affected is infected with the influenza virus, for example, at the time of measurement, the alpha-1-antitrypsin level may be higher for a short time as the immune system fights the acute, externally caused inflammation. It therefore makes sense to monitor the CRP value (an inflammation indicator) at the same time.
If a measured alpha-1-antitrypsin deficiency is present, we may arrange for a genetic test to be carried out to confirm this. Just a few drops of blood are enough. Such a diagnosis by genotyping is recommended for:
- young adults with emphysema,
- Blood relatives of people with alpha-1-antitrypsin deficiency,
- People with liver cirrhosis of unknown cause and
- People with chronic lung disease.
Alpha-1-antitrypsin deficiency: further examination procedures
In a sick person with symptoms that suggest alpha-1-antitrypsin deficiency, among other things, several other diseases are also possible. In order to weigh up the various clinical pictures against each other, as much evidence as possible must be collected. A physical examination may reveal discoloration of the skin. A bluish coloration indicates a lack of oxygen due to pulmonary emphysema, a yellowish coloration indicates liver damage. Imaging procedures such as X-rays or ultrasound reveal the exact condition of the internal organs, and tissue can also be removed for further analysis during a biopsy. The genetic test is the most informative and reliable diagnostic method in the case of alpha-1-antitrypsin deficiency.
Alpha-1-antitrypsin deficiency: prevention, early detection, prognosis
As alpha-1-antitrypsin deficiency is caused by a mutation in the genetic material, the disease cannot be prevented. However, the person affected has an immense influence on the effect of the enzyme inhibitor deficiency. This is one of the ways to avoid the most severe courses of disease with organ damage and life-limiting or even life-threatening conditions:
- Absolutely no smoking
- Avoidance of passive smoking
- Ensuring good air quality (e.g. avoiding dust, exhaust fumes)
- Regular exercise in the fresh air
- Maintaining a healthy body weight
- Healthy diet
- Prevention of colds
- Vaccination against influenza, pneumococcus
- Avoidance of psychological, social and professional stress
Early detection by genetic testing is possible at any time. You can have alpha-1-antitrypsin deficiency diagnosed using this test, even if you have no symptoms. As a preventive measure, you can lead a healthy and immune-boosting lifestyle and try to prevent infections. By strengthening your lungs, liver and immune system, you support your body in developing good overall health and, ideally, maintain a high quality of life – despite a genetic alpha-1-antitrypsin deficiency.
Progression and prognosis of alpha-1-antitrypsin deficiency
The consequences of alpha-1 antitrypsin deficiency depend on the severity of the genetic alteration:
- In the case of a heterozygous defect (i.e. only inherited from the mother or father), symptoms may not occur at all or only occur late or mildly.
- In the case of a homozygous disorder (inherited from both parents), the effects may already be very serious in childhood. Already after birth, around ten percent of newborns with alpha-1-antitrypsin deficiency suffer from inflammation of the liver with jaundice. Even if this episode of hepatitis is overcome, the liver remains susceptible to later damage.
Alpha-1-antitrypsin deficiency becomes particularly noticeable after the age of 30 and the symptoms become progressively more frequent and severe. The most common consequence of enzyme inhibitor deficiency is chronic obstructive pulmonary disease with subsequent pulmonary emphysema, an inflation of the lungs due to impaired function of the alveoli. In the worst case, this can increase to such an extent that respiratory failure, cardiac insufficiency or even multiple organ failure can occur. In addition to the lungs, which are mainly affected, the liver can also be damaged.
In old age, chronic hepatitis (inflammation of the liver) and even cirrhosis may develop, and in around 15 percent of cases, those affected develop liver cancer. In rare cases, painful lumps can form in the fatty tissue of the subcutis, and an alpha-1-antitrypsin deficiency may also lead to kidney failure, vascular inflammation or inflammation or scarring of the pancreas. Long-term chronic obstructive pulmonary disease or severe damage to the liver may require an organ transplant. If the liver is replaced, the alpha-1-antitrypsin deficiency is cured, as the formation of alpha-1-antitrypsin in the new liver proceeds normally due to the different genetic material.
Alpha-1-antitrypsin deficiency: treatment
The treatment of alpha-1-antitrypsin deficiency consists of various components. Whether it is successful also depends on the behavior of the person concerned. Only if they take their situation seriously can they have a positive influence on the course of the disease by adapting their lifestyle. If you want to counteract alpha-1-antitrypsin deficiency and its consequences, you need to take action yourself. Otherwise, the measures we have taken will not be effective.